pralatrexate 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
folic acid analogues 4117 146464-95-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • 10-Propargyl-10-deazaaminopterin
  • pralatrexate
  • folotyn
Pralatrexate is a folate analog metabolic inhibitor that competitively inhibits dihydrofolate reductase. It is also a competitive inhibitor for polyglutamylation by the enzyme folylpolyglutamyl synthetase. This inhibition results in the depletion of thymidine and other biological molecules the synthesis of which depends on single carbon transfer.
  • Molecular weight: 477.48
  • Formula: C23H23N7O5
  • CLOGP: 0.39
  • LIPINSKI: 1
  • HAC: 12
  • HDO: 5
  • TPSA: 207.30
  • ALOGS: -4.43
  • ROTB: 10
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 0.53 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2.70 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.33 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 15 hours Lombardo F, Berellini G, Obach RS

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2A,ACVR2B,AURKA,AXL,BRAF,BTK,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,ERBB2,FLT3,GRK2,ITK,MAP3K21,MAPK10,MAPK7,NTRK2,PDK1,PDK2,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PRKDC,SIK2,STK33,SYK,TEK 31
kinase-selectivity-class AXL,EIF2AK3,GRK2,MAPK7 4
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 0.530 Moderate 0.66
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 0 Moderate 0.66
rat-kpuu-brain Rat brain Kpuu 0.007 % Moderate 0.66

Approvals:

DateAgencyCompanyOrphan
July 3, 2017 PMDA Mundipharma KK
Sept. 24, 2009 FDA ALLOS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malignant neoplasm progression 127.28 52.29 42 623 106828 90520954
Quadriplegia 80.68 52.29 14 651 2217 90625565
Stomatitis 73.63 52.29 37 628 274661 90353121
Postictal state 72.94 52.29 12 653 1381 90626401
Mucosal inflammation 57.84 52.29 20 645 57605 90570177
Paralysis 52.72 52.29 13 652 11465 90616317

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Stomatitis 198.97 49.09 61 708 50268 42570298
Malignant neoplasm progression 125.57 49.09 53 716 108347 42512219
Mucosal inflammation 73.42 49.09 29 740 49345 42571221
Platelet count decreased 68.74 49.09 38 731 138543 42482023
Disease progression 62.05 49.09 36 733 143620 42476946
Neutrophil count decreased 53.62 49.09 25 744 63390 42557176

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malignant neoplasm progression 232.18 47.87 86 1338 174481 110413394
Stomatitis 212.25 47.87 91 1333 270151 110317724
Platelet count decreased 115.47 47.87 57 1367 230386 110357489
Mucosal inflammation 100.79 47.87 40 1384 96101 110491774
Neutrophil count decreased 82.22 47.87 37 1387 120904 110466971
Disease progression 65.38 47.87 40 1384 243994 110343881
Quadriplegia 64.16 47.87 14 1410 4113 110583762
Postictal state 59.40 47.87 12 1412 2434 110585441

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01BA05 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ANTIMETABOLITES
Folic acid analogues
FDA EPC N0000175584 Folate Analog Metabolic Inhibitor
CHEBI has role CHEBI:35221 antimetabolite
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50683 EC 1.5.1.3 (dihydrofolate reductase) inhibitor

Related Drugs by ATC class:

L01BA Folic acid analogues 3 drugs
methotrexatepemetrexedraltitrexed

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Peripheral T-cell lymphoma indication 109977009
Stomatitis contraindication 61170000 DOID:9637
Liver function tests abnormal contraindication 166603001
Impaired renal function disorder contraindication 197663003
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.61 acidic
pKa2 5.29 acidic
pKa3 13.13 acidic
pKa4 4.6 Basic
pKa5 4.51 Basic
pKa6 1.39 Basic
pKa7 0.14 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Dihydrofolate reductase Enzyme INHIBITOR Ki 7.35 IUPHAR CHEMBL
Proton-coupled folate transporter Transporter IC50 7.24 CHEMBL
Folate transporter 1 Transporter IC50 9.16 CHEMBL
Folate receptor alpha Membrane receptor IC50 6.78 CHEMBL

External reference:

IDSource
4029347 VUID
N0000180303 NUI
D05589 KEGG_DRUG
4029347 VANDF
C1721300 UMLSCUI
CHEBI:71223 CHEBI
CHEMBL1201746 ChEMBL_ID
DB06813 DRUGBANK_ID
C418863 MESH_SUPPLEMENTAL_RECORD_UI
6840 IUPHAR_LIGAND_ID
8560 INN_ID
A8Q8I19Q20 UNII
148121 PUBCHEM_CID
662019 RXNORM
168008 MMSL
26748 MMSL
364303 MMSL
d07492 MMSL
013258 NDDF
428598004 SNOMEDCT_US
429320009 SNOMEDCT_US
895675003 SNOMEDCT_US
A8Q8I19Q20 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Pralatrexate HUMAN PRESCRIPTION DRUG LABEL 1 43598-342 INJECTION 20 mg INTRAVENOUS ANDA 28 sections
Pralatrexate HUMAN PRESCRIPTION DRUG LABEL 1 43598-343 INJECTION 40 mg INTRAVENOUS ANDA 28 sections
Pralatrexate HUMAN PRESCRIPTION DRUG LABEL 1 65219-550 INJECTION 20 mg INTRAVENOUS NDA authorized generic 29 sections
Pralatrexate HUMAN PRESCRIPTION DRUG LABEL 1 65219-552 INJECTION 40 mg INTRAVENOUS NDA authorized generic 29 sections
Folotyn Human Prescription Drug Label 1 72893-003 INJECTION 20 mg INTRAVENOUS NDA 29 sections
Folotyn Human Prescription Drug Label 1 72893-005 INJECTION 40 mg INTRAVENOUS NDA 29 sections